Diabetes mellitus is a disease of major global importance, increasing in frequency at almost epidemic rates, such that the worldwide prevalence in 2006 is 170 million people and predicted to at least double over the next 10-15 years. Diabetes is characterized by a chronically raised blood glucose concentration (hyperglycemia), due to a relative or absolute lack of the pancreatic hormone, insulin. Within the healthy pancreas, beta cells, located in the islets of Langerhans, continuously produce and secrete insulin according to the blood glucose levels, maintaining near constant glucose levels in the body.
Much of the burden of the disease to the user and to health care resources is due to the long-term tissue complications, which affect both the small blood vessels (microangiopathy, causing eye, kidney and nerve damage) and the large blood vessels (causing accelerated atherosclerosis, with increased rates of coronary heart disease, peripheral vascular disease and stroke). The Diabetes Control and Complications Trial (DCCT) demonstrated that development and progression of the chronic complications of diabetes are greatly related to the degree of altered glycemia as quantified by determinations of glycohemoglobin (HbA1c). [DCCT Trial, N Engl J Med 1993; 329: 977-986, UKPDS Trial, Lancet 1998; 352: 837-853. BMJ 1998; 317, (7160): 703-13 and the EDIC Trial, N Engl J Med 2005; 353, (25): 2643-53]. Thus, maintaining normoglycemia by frequent glucose measurements and adjustment of insulin delivery accordingly can be of utmost importance.
Insulin pumps can deliver rapid acting insulin (i.e. Lispro, Aspart, etc.) 24 hours a day through a catheter placed under the skin. Rapid acting insulin effect begins in about 10 minutes, peaks at one to one and a half hours and ends in about two to six hours after the administration.
A simple rule can be applied to calculate the duration of insulin activity. It is often stated that 20% of a dose can be used each hour after bolus administration, so that after 5 hours there is no active insulin remaining in the body. FIG. 1 shows the insulin consumption according to the described rule (adapted from Using Insulin © 2003).
One of the major advantages of using insulin pumps is the convenience of insulin bolus administration at any desired time. However, boluses may overlap and it can be useful to know the amount of active insulin that is still “working” (hereinafter “residual insulin” or “RI”). Accumulation of insulin may lead to life-threatening hypoglycemia. This is especially important at bedtime since users are usually unaware of nocturnal hypoglycemia.
Many insulin pumps can apply the abovementioned rule to calculate the residual insulin and subtract the calculated value from current administered bolus. For example, if previously administered bolus was 6 IU, current (e.g., 2 hours after the previous bolus) administered bolus is 5 IU, RI 2 hours after the previously administered bolus is 3.6 IU, the actually delivered bolus should be 1.4 IU (5IU-3.6IU).
Application of the abovementioned rule can lead to over or under dosing due to significant individuality variability of insulin absorption and consumption. The assumption that the complete bolus absorption time (a state with no residual insulin, RI=0, hereinafter referred to as “residual insulin time” or “RI time”) is always 5 hours (20%/hour) ignores individual variability, and, as a result, may not be correct.
For example, if the entire bolus dose is absorbed within 3 hours (i.e. RI time is 3 hours), then following the table in FIG. 1 four hours after the bolus can lead to under dosing. If RI time is 6 hours, then following the table in FIG. 1 five hours after the bolus will lead to overdosing. Accurate, user specific assessment of the RI time can, therefore, be important for maintaining normoglycemia.